Pediatric Critical Care Medicine incorporates a multidisciplinary approach to address the medical needs of the most fragile population of critically ill and injured children. Fortunately, improvements in care over the past decades have impacted mortality for all PICU patients such that current annual rates at most academic, tertiary care centers are below 5%. However, certain disease processes, notably acute lung injury and sepsis, remain associated with significantly higher mortality rates as well as consume substantial health care resources. Despite this, the occurrences of these most challenging diseases do not occur sufficiently often at any one center to enable an effective, single-site study that will advance both our understanding and management of these diseases. Mindful of this reality, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) showed great wisdom in funding an infrastructure to address the need to create a multi-center research network, the Collaborative Pediatric Critical Care Research Network (CPCCRN). Our rapidly evolving program at the University of Michigan has made great strides in establishing a local infrastructure to allow us to actively participate in a number of network-based studies. In addition to possessing this infrastructure capacity, we also believe we have a team of investigators who can make important scientific and leadership contributions to this network. As a result, we are applying to continue as a participating site within CPCCRN to assist in executing investigations of pathobiology, management strategies, and the safety and efficacy of treatments for critically ill or injured children. As part of this application, we have submitted a Concept Proposal which reflects our intellectual capacity to contribute in a productive manner to CPCCRN (Aim 3). We hypothesize that an improved understanding of the mechanisms regulating gene expression associated with host immune dysfunction in the late phase of critical illnesses will identify novel therapeutic targets for further improving outcomes. This concept study is a reflection of our program's overall goal to contribute in a meaningful way to the on-going growth and success of a research network that is committed to improving both the short- and long-term outcomes of critically ill and injured children.